The broad objective of this proposal is to produce new information on the molecular structures and processes that underlie contraction and relaxation in cardiac and skeletal fast and slow muscle. Proteins of the contractile machinery (actin, myosin, troponin, tropomyosin) and of the sarcoplasmic reticulum and other muscle membranes will be studied by chemical, physico-chemical and enzymatic methods. The interaction of these proteins with each other, with metals, and nucleotides and - in the case of membrane proteins - with lipids, will be investigated with a view to obtaining insights into the processes that occur in muscle in vivo, particularly those of mechanico-chemical energy transduction of Ca2 ions dependent regulation and active metal ion processes. Efforts will be made to establish correlations between physiological events and molecular processes in cardiac and the different types of skeletal muscles and to obtain more information on the molecular processes that form the basis of muscle differentiation and the response of muscles to changed patterns of activity and innervation. It is hoped that some of the work can be extended to the investigation of the molecular processes on cardiac hypertrophy or failure and some pathological conditions of skeletal muscle. Some of the results expected to be obtained during the course of this work should also be of general interest for the better understanding of other complex systems involving protein-protein and protein-lipid interactions as well as various regulatory multi-stage processes. BIBLIOGRAPHIC REFERENCES: Potter, J., Nagy, B., Collins J., Seidel, J., Leavis, P., Lehrer, S. and Gergely, J. The Role of the Interaction of Ca2 ions with Troponin in the Regulation of Muscle Contraction, in "Molecular Basis of Motility," L. Heilmeyer, J.C. Ruegg and Wieland, Th., eds., Springer, p. 93, 1976. Leavis, P., Nagy, B. and Lehrer, S., Spectral Discrimination between the Two High Affinity Ca 2 ions Binding Sites of Troponin C, Abstract, Biophys. Soc., 1976, p. 71a.